The objectives of the proposed studies are to quantify longitudinally maternal metabolic responses to progressions of pregnancy and growth of the fetus. Specifically, the impact of pregnancy and alterations in fetal growth, e.g. in diabetes, upon whole body amino acid and glucose metabolism will be quantified using stable isotope tracer method. Data from our previous studies in human pregnancy have shown that while changes in energy delivering substrates, e.g. glucose and fatty acids, during pregnancy occur parallel with the energy requirements of the mother and growing conceptus, adaptive responses in protein/nitrogen metabolism appear in anticipation of the fetal needs. In addition, preliminary data suggest that (a) liver/splanchnic tissue may be an important organ system involved in the pregnancy related adaptation, and (b) amino acid transamination may be an important component of nitrogen conservation and accretion. The proposed studies are aimed at testing these two hypotheses. Multiple isotope tracers will be used simultaneously to quantify splanchnic extraction and metabolism of essential amino acids. Whole body kinetics of glutamine, a major nitrogen source for urea and for the fetus and its nitrogen source will be quantified. Since fetal macrosomia has continued to be a persistent problem in gestational diabetes despite rigorous intervention strategies, this clinical model of abnormal fetal growth will be evaluated for the changes in gluconeogenesis and amino acid metabolism. A recently developed novel method employing labeling of body water which has already been applied to normal pregnancy will be used to quantify gluconeogenesis in gestational diabetes. These studies will quantify kinetics of key nutrients and substrates in the whole body (mother and fetus) which can impact fetal growth. It is anticipated that these data will permit the development of intervention strategies for amelioration of aberrant fetal growth.